Effect of epileptic activity on outcome for critically ill patients
Authors: Nina Forss, Daniel Strbian
Journal: The Lancet Digital Health (2023)

Continuous electroencephalography (EEG) recordings of critically ill patients commonly show epileptiform activity. Such continuous EEG recordings have shown frequency of seizures to vary between 8% and 34%, most of which are non-convulsive.1Towne AR Waterhouse EJ Boggs JG et al.Prevalence of nonconvulsive status epilepticus in comatose patients.Neurology. 2000; 54: 340-345Crossref PubMed Google Scholar, 2Claassen J Mayer SA Kowalski RG Emerson RG Hirsch LJ Detection of electrographic seizures with continuous EEG monitoring in critically ill patients.Neurology. 2004; 62: 1743-1748Crossref PubMed Google Scholar, 3Friedman D Claassen J Hirsch LJ Continuous electroencephalogram monitoring in the intensive care unit.Anesth Analg. 2009; 109: 506-523Crossref PubMed Scopus (224) Google Scholar Other subtypes of epileptiform activity are also common in critically ill patients, including periodic and rhythmic patterns (eg, generalised and lateralised periodic discharges, generalised and lateralised rhythmic delta activity, and bilateral independent periodic discharges).4Rodriguez Ruiz A Vlachy J Lee JW et al.Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients.JAMA Neurol. 2017; 74: 181-188Crossref PubMed Scopus (159) Google Scholar Generalised epileptic seizures should be promptly and effectively treated to prevent escalation into status epilepticus, but treatment decisions for short-lasting epileptiform bursts or milder epileptic activities are not always straightforward.5Sánchez Fernández I Loddenkemper T Galanopoulou AS Moshé SL Should epileptiform discharges be treated?.Epilepsia. 2015; 56: 1492-1504Crossref PubMed Scopus (42) Google Scholar Several factors affect the decision making process regarding treatment intensity, including patient's age and previous diseases, cause of presenting disease, present general clinical condition, and duration of intensive care. The decisions are often made case-by-case on the basis of all forementioned factors.6Boggs JG Seizure management in the intensive care unit.Curr Treat Options Neurol. 2021; 23: 36Crossref PubMed Scopus (1) Google Scholar Growing evidence suggests that the presence of epileptic activity is associated with worse outcome,7Payne ET Zhao XY Frndova H et al.Seizure burden is independently associated with short term outcome in critically ill children.Brain. 2014; 137: 1429-1438Crossref PubMed Scopus (225) Google Scholar, 8De Marchis GM Pugin D Meyers E et al.Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome.Neurology. 2016; 86: 253-260Crossref PubMed Scopus (128) Google Scholar but it is not clear whether this is due to severity of underlying illness, medication side-effects, or worsening of epileptiform activity per se.9Rubinos C Reynolds AS Claassen J The ictal–interictal continuum: to treat or not to treat (and how)?.Neurocrit Care. 2018; 29: 3-8Crossref PubMed Scopus (0) Google Scholar The role of epileptiform activity in neurological outcome is very challenging to study, mostly due to a plethora of confounding factors and the complex interaction between the underlying disease, type of epileptiform activity, and antiepileptic medication. The study by Harsh Parikh and colleagues10Parikh H Hoffman K Sun H et al.Effects of epileptiform activity on discharge outcome in critically ill patients in the USA: a retrospective cross-sectional study.Lancet Digit Health. 2023; (published online June 7.)https://doi.org/10.1016/S2589-7500(23)00088-2Google Scholar in The Lancet Digital Health takes an important step forward in clarifying this clinically highly relevant question. Parikh and colleagues did a retrospective cross-sectional study with 995 patients, using a novel causal inference approach to adjust the treatment effect of antiseizure medication and to evaluate the effect of epileptiform activity on neurological outcome. Epileptiform activity was detected from continuous EEG with an automated algorithm, and several confounding factors were considered in the analysis, including pharmacokinetics and pharmacodynamics models. The patients’ drug responsiveness was estimated with a pharmacokinetic model adjusted for fixed drug half-lives, and with a pharmacodynamic model using the Hill coefficient and the dose to reduce epileptiform activity burden by 50%. All covariates (ie, demographics, clinical factors, admission diagnosis, and drug response parameters) were used for matching each patient to patients with similar covariates. Importantly, the matching was not based on proxies as is the case in the propensity-score approach, but rather based directly on these covariates. Although the approach of Parikh and colleagues might appear somewhat complicated, it allowed physicians to verify the quality of every analysis step instead of relying on purely data-driven models. The results of this study show that epileptiform activity burden correlates to neurological outcome after adjusting for antiseizure medications.10Parikh H Hoffman K Sun H et al.Effects of epileptiform activity on discharge outcome in critically ill patients in the USA: a retrospective cross-sectional study.Lancet Digit Health. 2023; (published online June 7.)https://doi.org/10.1016/S2589-7500(23)00088-2Google Scholar These results are in line with existing data showing that extensive epileptiform activity is associated with poor outcomes and provides outcome estimation based on quantification of the burden of epileptiform activity, which is clinically very useful. Patients with high levels of epileptic activity had a 22·27% (SD 0·92) increased chance of severe disability or death, and patients with moderate but long-lasting epileptic activity had a 13·52% (1·93) increased risk of a poor outcome. Subgroup analysis showed that the type of brain lesion mattered. Namely, patients with hypoxic–ischaemic encephalopathy or brain trauma were at higher risk of the worse outcome in response to a large maximum epileptiform activity burden. Parikh and colleagues included several confounding factors in their analysis, although it is very challenging to account for all possible confounding factors in this type of study. For example, possible spread and type of epileptiform activity is likely to be associated with the outcome. Here, all subtypes of epileptiform activity were included in evaluation of epileptiform activity burden, although, for example, lateralised periodic discharges have been shown to have a high association with seizures, whereas generalised rhythmic delta activity has not.4Rodriguez Ruiz A Vlachy J Lee JW et al.Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients.JAMA Neurol. 2017; 74: 181-188Crossref PubMed Scopus (159) Google Scholar Furthermore, in critically ill patients, several antiepileptic medications and anaesthetics are often used, particularly if EEG shows extensive epileptic activity. Interaction of different antiepileptics is common, and it might profoundly affect drug elimination and efficacy. Nevertheless, this study gives important insight to the complex association between epileptiform activity, drug effect, and neurological outcome. The results underline the importance of continuous EEG monitoring in patients in the intensive care unit and encourages timely treatment decisions in case short-lasting extensive or longer-lasting moderate epileptiform activity is observed. These promising results hopefully make way for larger, multicentre studies that would help to develop different treatment protocols tailored for patient groups with different CNS pathologies and other covariant factors. We declare no competing interests. Effects of epileptiform activity on discharge outcome in critically ill patients in the USA: a retrospective cross-sectional studyOur results suggest that interventions should put a higher priority on patients with an average epileptiform activity burden 10% or greater, and treatment should be more conservative when maximum epileptiform activity burden is low. Treatment should also be tailored to individual preadmission profiles because the potential for epileptiform activity to cause harm depends on age, medical history, and reason for admission. Full-Text PDF Open Access